Our research during the past three years has shown that proteolipids, nonpolar protein-acidic phospholipid complexes, are responsible for apatite nucleation in dental calculus matrices. Proteolipids are also responsible for calcification in microorganisms, bones and atherosclerosis. Synthetic analogues were prepared and used to study the calcification process. Acidic phospholipids via initial calcium binding are the most important feature of the complex. A naturally occurring metabolite, 2,3-diphosphoglyceric acid was found to be a potent inhibitor of proteolipid calcification. The proposed research has been designed to 1) test the hypothesis that proteolipids provide a membrane microenvironment which facilitates calcification and 2) evaluate 2,3-diphosphoglyceric acid as a potential agent for controlling human dental calculus formation.